ABSTRACT
A proinflammatory cytokine interleukin-6 (IL-6) plays an important role in the development, pathogenesis and outcome of SIRS, sepsis and septic shock. We have evaluated the role of the IL-6 gene polymorphisms in pediatric patients. A total of 421 consecutive pediatric patients admitted to the pediatric intensive care unit with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS) were studied together with 644 healthy controls. DNA was isolated and two IL-6 gene polymorphisms (G-174>C and G-572>C) were analyzed. The frequencies of both analyzed variants differ significantly between the group of patients and healthy controls (p = 0.02 for G-174>C and p = 0.049 for G-572>C). In addition, genetic analysis of the G-174>C IL-6 gene variant revealed significant differences between the subgroup of febrile patients and subgroup of septic shock (p = 0.0319) and between the subgroup of SIRS and septic shock (p = 0.038). In both cases the negative genotype was CC. No statistically significant differences for the IL-6 gene polymorphism G-572>C were found between the groups of patients with different diagnosis. IL-6 gene polymorphisms G-174>C and G-572>C could be the predictors of risk of development and/or the predictors of the severity of sepsis in children.
Subject(s)
Genetic Predisposition to Disease , Genetic Variation , Interleukin-6/genetics , Sepsis/genetics , Sepsis/immunology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Point Mutation , Sepsis/pathology , Shock, Septic/genetics , Shock, Septic/immunology , Shock, Septic/pathologyABSTRACT
OBJECTIVE: To evaluate the role of genetic polymorphisms of the bactericidal permeability increasing protein (BPI) in pediatric patients with sepsis. DESIGN: Prospective, single-center, case-control study at the pediatric intensive care unit (PICU) of a university hospital. PATIENTS: 345 consecutive pediatric patients admitted to the PICU with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS). INTERVENTIONS: DNA was isolated and two BPI gene polymorphisms BPI (G545 > C) Taq and BPI (A645[ > G) 216 were studied in patients and compared with healthy controls. MEASUREMENTS AND RESULTS: Genetic analysis of the BPI Taq gene revealed significant differences between healthy controls and the subgroup of febrile patients (p = 0.0243), the subgroup of SIRS and sepsis (p = 0.0101), and the subgroup of severe sepsis, septic shock, and MODS (p = 0.0027), respectively. No statistically significant differences for the BPI 216 gene polymorphism were found between patient and healthy control groups. A statistically significant predisposition to Gram-negative sepsis in patients carrying the BPI Taq GG variant together with the BPI 216 AG or GG variant was revealed (p = 0.0081), and these haplotypes were also associated with death due to sepsis-related complications. CONCLUSION: BPI Taq gene polymorphism is the accurate predictor of the severity of sepsis in children admitted to the PICU.
